POS0050 B CELL CHARACTERISTICS AT BASELINE PREDICT HUMORAL RESPONSE UPON SARS-CoV-2 VACCINATION AMONG PATIENTS TREATED WITH RITUXIMAB
Authors: A. L. Stefanski, H. Rincon-Arevalo, E. Schrezenmeier, K. Karberg, F. Szelinski, J. Ritter, B. Jahresdoerfer, H. Schrezenmeier, C. Ludwig, Y. Chen, A. Claußnitzer, A. Lino, T. Dörner
Journal: Annals of the Rheumatic Diseases (2022)

Background Vaccination is considered efficient in controlling infections incl. SARS-CoV-2. Prior studies showed that patients receiving rituximab (RTX) with low B cell counts are at increased infectious risk (1) and risk of inadequate vaccination responses (2, 3). Thus, the ability to further define and predict vaccination responses in these patients may guide their optimal protection. Objectives To assess predictive biomarkers of vaccination responses upon SARS-CoV-2 vaccination in RTX treated patients. Methods B cell characteristics before vaccination were evaluated to predict responses in 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. 11 patients with rheumatoid arthritis on other therapies (RA), 11 kidney transplant recipients (KTR) and 15 healthy volunteers (HC) served as controls. A multidimensional analysis of B cell subsets and a correlation matrix were performed to identify predictive biomarkers. Results Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were validated at baseline. Here, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) comprised naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells (Figure 1). Moreover, there was a positive correlation between neutralizing antibodies and absolute B cell numbers with B cells expressing HLA-DR and CXCR5 (involved in antigen presentation and germinal center formation) as well as an inverse correlation with CD95 expression and CD21low expression (marker for activation and exhaustion) on B cells. Conclusion Substantial repopulation of naïve B cells upon RTX therapy appears to be essential for an adequate vaccination response requiring germinal center formation. In contrast, expression of exhaustion markers (CD21low, CXCR5-, CD95+) indicate negative predictors of vaccination responses. These results may guide optimized vaccination strategies in RTX treated patients clearly requiring antigen-inexperienced B cells for appropriate protection. References [1]Sparks JA, Wallace ZS, Seet AM, Gianfrancesco MA, Izadi Z, Hyrich KL, et al. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry. Annals of the Rheumatic Diseases. 2021;80(9):1137-46. [2]Stefanski AL, Rincon-Arevalo H, Schrezenmeier E, Karberg K, Szelinski F, Ritter J, et al. B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab. Arthritis &amp; Rheumatology. Accepted Author Manuscript. [3]Mrak D, Tobudic S, Koblischke M, Graninger M, Radner H, Sieghart D, et al. SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity. Annals of the rheumatic diseases. 2021;80(10):1345-50. Disclosure of Interests None declared